In a broad sense, the objectives of this research are to understand biological processes on a molecular level. The focus of the proposed work is on the action of the toxin from Bacillus sphaericus that kills mosquito larvae after ingestion. This toxin acts as a binary system involving two subunits with molecular weights of 42 and 51 kDa ahd has a very narrow host range against disease vectors, including Anopheles that is a carrier of malaria. The general goal of the proposed work is to understand the mechanism of this toxin by combining the determination of the three dimensional structure with functional investigations involving mutagenesis studies. The specific objectives are: 1. To complete the determination of the three dimensional structure of the 51 kDa protein at a resolution limit of 2.6 A. 2. To improve the quality of the crystals, collect data at a resolution limit of 2.2A, and determine the structure at higher resolution. 3. To crystallize and determine the structure of the binary complex. 4. To determine the structure of the toxin from different species of B. Sphaericus that have significantly different toxicity. 5. To perform structural studies on a second toxin from B. Sphaericus. 6. To characterize a set of mutants design to elucidate the receptor binding region of the toxin and the mode of toxicity. These studies will involve both structural and functional studies. These projects should allow us to model the binding of the toxin to the membrane and consequential disruption of the membrane. This model should lead to a better general understand of the general mechanism of toxins. Of particular interest is understanding the factors that cause the very narrow host range binding of this toxin. These results should contribute towards the development of effective agents that specifically target disease carrying mosquitoes.